N-{4-[4-(4-Fluoro­phen­yl)-1-methyl-2-[(R)-methyl­sulfin­yl]-1H-imidazol-5-yl]-2-pyridyl}acetamide dihydrate

Bühler, S.; Schollmeyer, D.; Hauser, D.; Albrecht, W.; Laufer, S.

doi:10.1107/S1600536809051873

organic compounds

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ISSN: 2056-9890

Volume 66| Part 1| January 2010| Page o121

doi:10.1107/S1600536809051873

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N-{4-[4-(4-Fluorophenyl)-1-methyl-2-[(R)-methylsulfinyl]-1H-imidazol-5-yl]-2-pyridyl}acetamide dihydrate

Stefanie Bühler,^a Dieter Schollmeyer,^b Dominik Hauser,^a Wolfgang Albrecht ^c and Stefan Laufer ^a ^*

^aEberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, ^bUniversity Mainz, Institut of Organic Chemistry, Duesbergweg 10-14, 55099 Mainz, Germany, and ^cc-a-i-r biosciences GmbH, Paul-Ehrlich-Str. 15, 72076 Tübingen, Germany
^*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 26 November 2009; accepted 2 December 2009; online 12 December 2009)

In the crystal structure of the title compound, C₁₈H₁₇FN₄O₂S·2H₂O, the organic molecules are linked by intermolecular O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds with the water molecules, generating a three-dimensional network. The imidazole ring system forms a dihedral angle of 24.9 (2)° with the 4-fluorophenyl ring. The pyridine ring is oriented approximately perpendicular [72.24 (8)°] to the imidazole ring system.

Related literature

For general background and the biological activity of chiral sulfoxides and their potential use as therapeutic agents, see: Jia et al., (2004 ). Sulfoxide enantiomers can differ in their pharmacodynamic and/or pharmacokinetic properties, see: Lu (2007 ). For the preparation of tri- and tetrasubstituted 2-thioimidazoles, see: Wagner et al. (2003 ); Laufer, Hauser, Domeyer et al. (2008 ); Laufer, Hauser & Liedtke (2008 ).

Experimental

Crystal data

C₁₈H₁₇FN₄O₂S·2H₂O
M_r = 408.45
Orthorhombic, P 2₁ 2₁ 2₁
a = 5.8178 (2) Å
b = 14.3233 (5) Å
c = 23.3694 (9) Å
V = 1947.37 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 193 K
0.50 × 0.10 × 0.10 mm

Data collection

Bruker SMART APEXII diffractometer
10703 measured reflections
4628 independent reflections
2634 reflections with I > 2σ(I)
R_int = 0.089

Refinement

R[F² > 2σ(F²)] = 0.046
wR(F²) = 0.099
S = 0.84
4628 reflections
256 parameters
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.30 e Å⁻³
Absolute structure: Flack (1983 ), 1949 Friedel pairs
Flack parameter: −0.08 (11)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N24—H24⋯O15ⁱ	0.91	2.08	2.983 (3)	177
O1L—H1L⋯O26ⁱⁱ	0.94	1.90	2.825 (3)	169
O1L—H2L⋯O15	0.85	2.00	2.775 (3)	151
O2L—H3L⋯O1L	0.84	1.90	2.743 (4)	177
O2L—H4L⋯N2	0.84	2.51	3.193 (3)	138
Symmetry codes: (i) $[-x+{\script{1\over 2}}, -y+1, z-{\script{1\over 2}}]$ ; (ii) $[-x, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Data collection: APEX2 (Bruker, 2006 ); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: PLATON (Spek, 2009 ); software used to prepare material for publication: PLATON.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809051873/nc2170sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809051873/nc2170Isup2.hkl

checkCIF report

Comment top

Many chiral sulfoxides exhibit interesting biological activities and show promise as therapeutic agents (Jia et al., 2004). The title compound, N-(4-(4-(4-fluorophenyl)-1-methyl-2-((R)-methylsulfinyl)-1H-imidazol-5-yl) pyridin-2-yl)acetamide, was prepared in the course of our studies on tri- and tetrasubstituted 2-thioimidazoles as p38 mitogen-activated protein (MAP) kinase inhibitors (Wagner et al., 2003, Laufer, Hauser, Domeyer et al.,2008); Laufer, Hauser & Liedtke, 2008). The oxidation of the sulfide N-(4-(4-(4-fluorophenyl)-1-methyl-2-(methylthio)-1H-imidazol-5-yl)pyridin-2- yl)acetamide with sodium periodate as oxidant yields the corresponding sulfoxide N-(4-(4-(4-fluorophenyl)-1-methyl-2-(methylsulfinyl)-1H-imidazol-5-yl) pyridin-2-yl)acetamide. This compound has a centre of asymmetry in the sulfur atom meaning that two sulfoxide enantiomers exist, which can differ in pharmacodynamic and/or pharmacokinetic properties (Lu, 2007). The both enantiomers were separated by enantioselective preparative HPLC. To identify the absolute configurations of the enantiomers according to the Cahn-Ingold-Prelog-nomenclature X-ray analysis was used. In this article we present the X-ray data of the first eluted enantiomer I. The analysis of the crystal structure shows that the N24 amino- group of the acetamide moiety of the one imidazole-molecule interact with another imidazole ring system by the building of one intermolecular hydrogen bond N—H···O to the sulfoxide oxygen-atom O15, whereas the O15···H24 distance is 2.08 Å. Furthermore, the carbonyl-oxygen atom O26 of the acetamide-moiety of a third imidazole molecule is linked over two water molecules to the sulfoxide oxygen-atom O15 and to the nitrogen atom N2 of the imidazole core by the building of intermolecular O1L—H1L···O26 (1.90 Å), O1L—H2L···O15 (2.00 Å) and O2L—H4L···N2 (2.51 Å) hydrogen bonds. The imidazole ring system forms a dihedral angle of 24.9 (1)° to the 4-fluorophenyl ring. The pyridine ring is oriented approximately perpendicular (72.24 (8)°) to the imidazole ring system. According to the Cahn-Ingold-Prelog-nomenclature the first eluted enantiomer I is (R)-configurated.

Related literature top

For general background the biological activity of chiral sulfoxides and their potential use as therapeutic agents, see: Jia et al., (2004). Sulfoxide enantiomers can differ in their pharmacodynamic and/or pharmacokinetic properties, see: Lu (2007). For the preparation of tri- and tetrasubstituted 2-thioimidazoles, see: Wagner et al. (2003); Laufer, Hauser, Domeyer et al. (2008); Laufer, Hauser & Liedtke (2008).

Experimental top

N-(4-(4-(4-fluorophenyl)-1-methyl-2-(methylthio)-1H-imidazol-5-yl)pyridin-2- yl)acetamide (3.56 g, 10 mmol) was dissolved in a mixture of THF (30 ml) and acetone (58 ml), and water (45 ml) was added. The mixture was stirred at T = 313 K, and an aqueous solution of sodium periodate (4.01 g, 18.4 mmol in 65 ml water) was added dropwise. The reaction mixture was heated at T = 338 K. The progress was again monitored until HPLC analysis (C8 Betasil, MeOH/ 0.01 M KH₂PO₄, pH = 2,3) indicated complete conversion. After cooling to rt, the organic solvents were removed under reduced pressure and a precipitate dropped down, which was filtered off and washed with water and isopropylether. The crude product was purified by recrystallization from ethylacetate to yield 3.02 g (81.2%) of the colorless racemic product N-(4-(4-(4-fluorophenyl)-1-methyl-2-(methylsulfinyl)-1H-imidazol-5-yl)pyridin-2-yl)acetamide. The both enantiomers were isolated by enantioselective preparative HPLC (Daicel CHIRALPAK AD, CH₂Cl₂ / MeOH/ TEA 98: 2: 0.1). Suitable crystals of the first eluted enantiomer I for X-ray were obtained by slow evaporation at T = 298 K of a solution of ethanol.

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top

Fig. 1. View of compound I. Displacement ellipsoids are drawn at the 50% probability level.

N-{4-[4-(4-Fluorophenyl)-1-methyl-2-[(R)-methylsulfinyl]- 1H-imidazol-5-yl]-2-pyridyl}acetamide dihydrate top

Crystal data top

C₁₈H₁₇FN₄O₂S·2H₂O	F(000) = 856
M_r = 408.45	D_x = 1.393 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71069 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1669 reflections
a = 5.8178 (2) Å	θ = 2.9–23.5°
b = 14.3233 (5) Å	µ = 0.21 mm⁻¹
c = 23.3694 (9) Å	T = 193 K
V = 1947.37 (12) Å³	Needle, colourless
Z = 4	0.50 × 0.10 × 0.10 mm

Data collection top

Bruker SMART APEXII diffractometer	2634 reflections with I > 2σ(I)
Radiation source: sealed Tube	R_int = 0.089
Graphite monochromator	θ_max = 27.9°, θ_min = 1.7°
CCD scan	h = −7→7
10703 measured reflections	k = −18→15
4628 independent reflections	l = −24→30

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.046	H-atom parameters constrained
wR(F²) = 0.099	w = 1/[σ²(F_o²) + (0.0293P)²] where P = (F_o² + 2F_c²)/3
S = 0.84	(Δ/σ)_max = 0.001
4628 reflections	Δρ_max = 0.27 e Å⁻³
256 parameters	Δρ_min = −0.30 e Å⁻³
0 restraints	Absolute structure: Flack (1983), 1949 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.08 (11)

Crystal data top

C₁₈H₁₇FN₄O₂S·2H₂O	V = 1947.37 (12) Å³
M_r = 408.45	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 5.8178 (2) Å	µ = 0.21 mm⁻¹
b = 14.3233 (5) Å	T = 193 K
c = 23.3694 (9) Å	0.50 × 0.10 × 0.10 mm

Data collection top

Bruker SMART APEXII diffractometer	2634 reflections with I > 2σ(I)
10703 measured reflections	R_int = 0.089
4628 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.046	H-atom parameters constrained
wR(F²) = 0.099	Δρ_max = 0.27 e Å⁻³
S = 0.84	Δρ_min = −0.30 e Å⁻³
4628 reflections	Absolute structure: Flack (1983), 1949 Friedel pairs
256 parameters	Absolute structure parameter: −0.08 (11)
0 restraints

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	−0.0028 (5)	0.38294 (18)	0.67677 (10)	0.0247 (6)
N2	0.0086 (5)	0.38684 (16)	0.73573 (9)	0.0301 (6)
C3	0.1670 (5)	0.44957 (18)	0.74681 (10)	0.0299 (7)
N4	0.2625 (4)	0.48701 (15)	0.69850 (7)	0.0276 (5)
C5	0.1496 (5)	0.44518 (18)	0.65318 (10)	0.0244 (6)
C6	−0.1622 (5)	0.31718 (18)	0.64897 (11)	0.0265 (7)
C7	−0.1212 (6)	0.2827 (2)	0.59361 (11)	0.0334 (7)
H7	0.0139	0.3008	0.5736	0.040*
C8	−0.2761 (6)	0.2227 (2)	0.56802 (13)	0.0406 (8)
H8	−0.2504	0.2003	0.5303	0.049*
C9	−0.4667 (6)	0.1961 (2)	0.59797 (14)	0.0428 (9)
C10	−0.5117 (6)	0.2250 (2)	0.65250 (13)	0.0391 (8)
H10	−0.6438	0.2036	0.6725	0.047*
C11	−0.3591 (5)	0.2864 (2)	0.67776 (12)	0.0326 (7)
H11	−0.3885	0.3082	0.7154	0.039*
F13	−0.6195 (4)	0.13680 (13)	0.57211 (9)	0.0687 (6)
S14	0.25518 (17)	0.48524 (5)	0.81652 (3)	0.0404 (2)
O15	0.3625 (4)	0.40219 (16)	0.84497 (7)	0.0490 (6)
C16	−0.0249 (7)	0.4982 (3)	0.84489 (11)	0.0636 (12)
H16C	−0.0151	0.5104	0.8861	0.095*
H16B	−0.1127	0.4408	0.8383	0.095*
H16A	−0.1020	0.5506	0.8260	0.095*
C17	0.4374 (6)	0.5604 (2)	0.69480 (12)	0.0439 (9)
H17A	0.4180	0.6041	0.7267	0.066*
H17B	0.4205	0.5940	0.6585	0.066*
H17C	0.5906	0.5321	0.6967	0.066*
C18	0.2057 (5)	0.47072 (17)	0.59317 (9)	0.0244 (6)
C19	0.4114 (5)	0.44302 (19)	0.56902 (11)	0.0285 (7)
H19	0.5209	0.4092	0.5909	0.034*
C20	0.4555 (6)	0.4653 (2)	0.51252 (11)	0.0331 (7)
H20	0.5962	0.4448	0.4961	0.040*
N21	0.3106 (4)	0.51404 (17)	0.47977 (8)	0.0294 (6)
C22	0.1152 (5)	0.54307 (19)	0.50371 (11)	0.0262 (7)
C23	0.0530 (5)	0.52212 (19)	0.56027 (10)	0.0264 (6)
H23	−0.0896	0.5426	0.5756	0.032*
N24	−0.0213 (4)	0.59582 (16)	0.46634 (9)	0.0314 (6)
H24	0.0221	0.5970	0.4291	0.047*
C25	−0.1937 (6)	0.65639 (19)	0.47982 (12)	0.0327 (7)
O26	−0.2713 (4)	0.66543 (13)	0.52821 (8)	0.0405 (5)
C27	−0.2867 (7)	0.7123 (2)	0.43046 (12)	0.0530 (10)
H27A	−0.2501	0.7784	0.4361	0.080*
H27C	−0.4538	0.7044	0.4284	0.080*
H27B	−0.2166	0.6904	0.3948	0.080*
O1L	0.2647 (6)	0.21319 (16)	0.85452 (9)	0.0726 (8)
H1L	0.2717	0.2057	0.8945	0.109*
H2L	0.2448	0.2723	0.8557	0.109*
O2L	0.0400 (5)	0.16661 (18)	0.75536 (11)	0.0795 (9)
H3L	0.1051	0.1806	0.7863	0.119*
H4L	−0.0357	0.2127	0.7435	0.119*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0296 (16)	0.0238 (15)	0.0207 (13)	0.0027 (13)	−0.0021 (14)	0.0000 (11)
N2	0.0400 (16)	0.0291 (14)	0.0211 (11)	−0.0024 (12)	−0.0021 (12)	0.0038 (10)
C3	0.0408 (19)	0.0302 (15)	0.0186 (13)	−0.0020 (14)	−0.0058 (14)	0.0009 (11)
N4	0.0324 (13)	0.0299 (12)	0.0206 (10)	−0.0038 (13)	−0.0037 (12)	0.0004 (9)
C5	0.0266 (17)	0.0261 (14)	0.0206 (13)	0.0042 (13)	−0.0028 (13)	0.0002 (11)
C6	0.0312 (19)	0.0238 (14)	0.0245 (13)	0.0029 (13)	−0.0061 (14)	0.0038 (11)
C7	0.0332 (18)	0.0328 (17)	0.0341 (16)	0.0031 (16)	−0.0017 (15)	−0.0034 (13)
C8	0.044 (2)	0.0349 (17)	0.0434 (16)	0.0021 (19)	−0.0093 (19)	−0.0141 (14)
C9	0.036 (2)	0.0325 (19)	0.060 (2)	−0.0051 (17)	−0.0175 (19)	−0.0050 (16)
C10	0.0320 (19)	0.0342 (18)	0.0512 (19)	−0.0045 (16)	−0.0054 (17)	0.0131 (15)
C11	0.0333 (18)	0.0325 (17)	0.0318 (15)	0.0013 (15)	−0.0020 (15)	0.0071 (13)
F13	0.0562 (14)	0.0548 (13)	0.0950 (15)	−0.0195 (12)	−0.0165 (14)	−0.0227 (12)
S14	0.0586 (5)	0.0411 (4)	0.0215 (3)	−0.0017 (5)	−0.0099 (4)	−0.0032 (3)
O15	0.0636 (17)	0.0592 (15)	0.0243 (10)	0.0236 (14)	−0.0124 (11)	−0.0030 (10)
C16	0.072 (3)	0.091 (3)	0.0272 (15)	0.030 (3)	−0.0050 (18)	−0.0117 (18)
C17	0.048 (2)	0.046 (2)	0.0385 (17)	−0.0163 (17)	−0.0022 (17)	0.0006 (14)
C18	0.0316 (18)	0.0237 (14)	0.0180 (12)	−0.0032 (14)	−0.0011 (12)	−0.0002 (10)
C19	0.0288 (17)	0.0322 (17)	0.0243 (14)	0.0034 (14)	−0.0031 (14)	0.0050 (12)
C20	0.0310 (18)	0.040 (2)	0.0288 (15)	0.0034 (15)	0.0038 (14)	0.0011 (13)
N21	0.0311 (15)	0.0318 (13)	0.0254 (11)	0.0066 (12)	0.0012 (11)	0.0013 (10)
C22	0.0313 (18)	0.0258 (16)	0.0214 (13)	−0.0029 (14)	−0.0005 (13)	−0.0007 (11)
C23	0.0289 (17)	0.0288 (16)	0.0214 (13)	0.0013 (14)	0.0018 (12)	−0.0020 (12)
N24	0.0385 (16)	0.0373 (15)	0.0185 (11)	0.0101 (14)	0.0004 (12)	0.0032 (10)
C25	0.037 (2)	0.0295 (16)	0.0318 (15)	0.0049 (15)	−0.0035 (15)	−0.0010 (12)
O26	0.0463 (14)	0.0462 (12)	0.0289 (10)	0.0108 (13)	0.0015 (12)	−0.0037 (9)
C27	0.065 (3)	0.052 (2)	0.0415 (17)	0.026 (2)	−0.006 (2)	0.0082 (15)
O1L	0.105 (2)	0.0615 (16)	0.0516 (13)	0.0245 (19)	0.0045 (17)	−0.0070 (12)
O2L	0.086 (2)	0.0676 (18)	0.0850 (18)	−0.0002 (17)	−0.0200 (19)	0.0271 (15)

Geometric parameters (Å, º) top

C1—C5	1.373 (4)	C17—H17A	0.9800
C1—N2	1.380 (3)	C17—H17B	0.9800
C1—C6	1.473 (4)	C17—H17C	0.9800
N2—C3	1.313 (4)	C18—C19	1.381 (4)
C3—N4	1.368 (3)	C18—C23	1.386 (4)
C3—S14	1.783 (3)	C19—C20	1.382 (3)
N4—C5	1.383 (3)	C19—H19	0.9500
N4—C17	1.465 (4)	C20—N21	1.336 (3)
C5—C18	1.485 (3)	C20—H20	0.9500
C6—C11	1.400 (4)	N21—C22	1.333 (3)
C6—C7	1.405 (4)	C22—N24	1.402 (3)
C7—C8	1.382 (4)	C22—C23	1.403 (3)
C7—H7	0.9500	C23—H23	0.9500
C8—C9	1.365 (5)	N24—C25	1.363 (4)
C8—H8	0.9500	N24—H24	0.9072
C9—C10	1.365 (4)	C25—O26	1.224 (3)
C9—F13	1.370 (4)	C25—C27	1.505 (4)
C10—C11	1.382 (4)	C27—H27A	0.9800
C10—H10	0.9500	C27—H27C	0.9800
C11—H11	0.9500	C27—H27B	0.9800
S14—O15	1.499 (2)	O1L—H1L	0.9410
S14—C16	1.769 (4)	O1L—H2L	0.8545
C16—H16C	0.9800	O2L—H3L	0.8400
C16—H16B	0.9800	O2L—H4L	0.8400
C16—H16A	0.9800

C5—C1—N2	110.1 (2)	H16C—C16—H16A	109.5
C5—C1—C6	130.1 (2)	H16B—C16—H16A	109.5
N2—C1—C6	119.8 (2)	N4—C17—H17A	109.5
C3—N2—C1	105.0 (2)	N4—C17—H17B	109.5
N2—C3—N4	113.0 (2)	H17A—C17—H17B	109.5
N2—C3—S14	125.3 (2)	N4—C17—H17C	109.5
N4—C3—S14	121.7 (2)	H17A—C17—H17C	109.5
C3—N4—C5	105.6 (2)	H17B—C17—H17C	109.5
C3—N4—C17	127.7 (2)	C19—C18—C23	118.7 (2)
C5—N4—C17	126.5 (2)	C19—C18—C5	120.3 (2)
C1—C5—N4	106.3 (2)	C23—C18—C5	120.9 (2)
C1—C5—C18	132.9 (2)	C18—C19—C20	119.0 (3)
N4—C5—C18	120.8 (2)	C18—C19—H19	120.5
C11—C6—C7	118.1 (3)	C20—C19—H19	120.5
C11—C6—C1	120.3 (2)	N21—C20—C19	123.4 (3)
C7—C6—C1	121.6 (3)	N21—C20—H20	118.3
C8—C7—C6	120.4 (3)	C19—C20—H20	118.3
C8—C7—H7	119.8	C22—N21—C20	117.4 (2)
C6—C7—H7	119.8	N21—C22—N24	112.9 (2)
C9—C8—C7	118.8 (3)	N21—C22—C23	123.3 (3)
C9—C8—H8	120.6	N24—C22—C23	123.8 (3)
C7—C8—H8	120.6	C18—C23—C22	118.1 (3)
C10—C9—C8	123.4 (3)	C18—C23—H23	121.0
C10—C9—F13	118.4 (3)	C22—C23—H23	121.0
C8—C9—F13	118.3 (3)	C25—N24—C22	128.0 (2)
C9—C10—C11	117.9 (3)	C25—N24—H24	114.5
C9—C10—H10	121.0	C22—N24—H24	116.8
C11—C10—H10	121.0	O26—C25—N24	123.5 (2)
C10—C11—C6	121.4 (3)	O26—C25—C27	121.3 (3)
C10—C11—H11	119.3	N24—C25—C27	115.2 (3)
C6—C11—H11	119.3	C25—C27—H27A	109.5
O15—S14—C16	107.50 (16)	C25—C27—H27C	109.5
O15—S14—C3	107.32 (12)	H27A—C27—H27C	109.5
C16—S14—C3	96.18 (15)	C25—C27—H27B	109.5
S14—C16—H16C	109.5	H27A—C27—H27B	109.5
S14—C16—H16B	109.5	H27C—C27—H27B	109.5
H16C—C16—H16B	109.5	H1L—O1L—H2L	94.9
S14—C16—H16A	109.5	H3L—O2L—H4L	109.5

C5—C1—N2—C3	−0.7 (3)	F13—C9—C10—C11	−178.6 (3)
C6—C1—N2—C3	178.7 (3)	C9—C10—C11—C6	−1.1 (4)
C1—N2—C3—N4	−0.4 (3)	C7—C6—C11—C10	−0.9 (4)
C1—N2—C3—S14	179.4 (2)	C1—C6—C11—C10	179.8 (3)
N2—C3—N4—C5	1.4 (3)	N2—C3—S14—O15	64.5 (3)
S14—C3—N4—C5	−178.5 (2)	N4—C3—S14—O15	−115.7 (2)
N2—C3—N4—C17	177.9 (3)	N2—C3—S14—C16	−46.0 (3)
S14—C3—N4—C17	−2.0 (4)	N4—C3—S14—C16	133.8 (3)
N2—C1—C5—N4	1.5 (3)	C1—C5—C18—C19	−107.8 (4)
C6—C1—C5—N4	−177.8 (3)	N4—C5—C18—C19	71.7 (3)
N2—C1—C5—C18	−178.9 (3)	C1—C5—C18—C23	71.8 (4)
C6—C1—C5—C18	1.8 (5)	N4—C5—C18—C23	−108.7 (3)
C3—N4—C5—C1	−1.7 (3)	C23—C18—C19—C20	−1.7 (4)
C17—N4—C5—C1	−178.2 (3)	C5—C18—C19—C20	177.9 (3)
C3—N4—C5—C18	178.7 (2)	C18—C19—C20—N21	1.2 (4)
C17—N4—C5—C18	2.1 (4)	C19—C20—N21—C22	0.8 (4)
C5—C1—C6—C11	−155.5 (3)	C20—N21—C22—N24	178.2 (2)
N2—C1—C6—C11	25.2 (4)	C20—N21—C22—C23	−2.3 (4)
C5—C1—C6—C7	25.2 (5)	C19—C18—C23—C22	0.3 (4)
N2—C1—C6—C7	−154.0 (3)	C5—C18—C23—C22	−179.3 (2)
C11—C6—C7—C8	2.1 (4)	N21—C22—C23—C18	1.8 (4)
C1—C6—C7—C8	−178.6 (3)	N24—C22—C23—C18	−178.8 (3)
C6—C7—C8—C9	−1.3 (4)	N21—C22—N24—C25	−160.2 (3)
C7—C8—C9—C10	−0.8 (5)	C23—C22—N24—C25	20.3 (4)
C7—C8—C9—F13	179.8 (3)	C22—N24—C25—O26	−8.5 (5)
C8—C9—C10—C11	2.0 (5)	C22—N24—C25—C27	172.0 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N24—H24···O15ⁱ	0.91	2.08	2.983 (3)	177
O1L—H2L···O15	0.85	2.00	2.775 (3)	151
O1L—H1L···O26ⁱⁱ	0.94	1.90	2.825 (3)	169
O2L—H3L···O1L	0.84	1.90	2.743 (4)	177
O2L—H4L···N2	0.84	2.51	3.193 (3)	138

Symmetry codes: (i) −x+1/2, −y+1, z−1/2; (ii) −x, y−1/2, −z+3/2.

Experimental details

Crystal data
Chemical formula	C₁₈H₁₇FN₄O₂S·2H₂O
M_r	408.45
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	193
a, b, c (Å)	5.8178 (2), 14.3233 (5), 23.3694 (9)
V (Å³)	1947.37 (12)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.21
Crystal size (mm)	0.50 × 0.10 × 0.10

Data collection
Diffractometer	Bruker SMART APEXII diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	10703, 4628, 2634
R_int	0.089
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.046, 0.099, 0.84
No. of reflections	4628
No. of parameters	256
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.27, −0.30
Absolute structure	Flack (1983), 1949 Friedel pairs
Absolute structure parameter	−0.08 (11)

Computer programs: APEX2 (Bruker, 2006), SAINT (Bruker, 2006), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N24—H24···O15ⁱ	0.91	2.08	2.983 (3)	177
O1L—H2L···O15	0.85	2.00	2.775 (3)	151
O1L—H1L···O26ⁱⁱ	0.94	1.90	2.825 (3)	169
O2L—H3L···O1L	0.84	1.90	2.743 (4)	177
O2L—H4L···N2	0.84	2.51	3.193 (3)	138

Symmetry codes: (i) −x+1/2, −y+1, z−1/2; (ii) −x, y−1/2, −z+3/2.

Acknowledgements

The authors thank the Federal Ministry of Education and Research, Germany, Merckle GmbH, Ulm, Germany, and the Fonds der Chemischen Industrie, Germany, for their generous support of this work.

References

Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115–119. Web of Science CrossRef CAS IUCr Journals Google Scholar
Bruker (2006). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Jia, X., Li, X., Xu, L., Li, Y., Shi, Q., Au-Yeung, T. T.-L., Yip, C. W., Yao, X. & Chan, A. S. C. (2004). Adv. Synth. Catal. 346, 723–726. Web of Science CrossRef CAS Google Scholar
Laufer, S. A., Hauser, D. R. J., Domeyer, D. M., Kinkel, K. & Liedtke, A. J. (2008). J. Med. Chem. 51, 4122–4149. Web of Science CrossRef PubMed CAS Google Scholar
Laufer, S. A., Hauser, D. R. J. & Liedtke, A. J. (2008). Synthesis, 2, 253–266. Web of Science CrossRef Google Scholar
Lu, H. (2007). Exp. Opin. Drug Metab. Toxicol. 3, 149–158. CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wagner, G. K., Kotschenreuther, D., Zimmermann, W. & Laufer, S. A. (2003). J. Org. Chem. 68, 4527–4530. Web of Science CrossRef PubMed CAS Google Scholar

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Volume 66| Part 1| January 2010| Page o121

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

N-{4-[4-(4-Fluoro­phen­yl)-1-methyl-2-[(R)-methyl­sulfin­yl]-1H-imidazol-5-yl]-2-pyridyl}acetamide dihydrate

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Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

N-{4-[4-(4-Fluorophenyl)-1-methyl-2-[(R)-methylsulfinyl]-1H-imidazol-5-yl]-2-pyridyl}acetamide dihydrate